Investigation of the Effect on the Albumin Binding Moiety for the Pharmacokinetic Properties of <sup>68</sup>Ga-, <sup>205/206</sup>Bi-, and <sup>177</sup>Lu-Labeled NAPamide-Based Radiopharmaceuticals
Although radiolabeled alpha-melanocyte stimulating hormone-analogue NAPamide derivatives are valuable melanoma-specific diagnostic probes, their rapid elimination kinetics and high renal uptake may preclude them from being used in clinical settings. We aimed at improving the pharmacokinetics of radi...
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MDPI AG
2023-09-01
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| Online Access: | https://www.mdpi.com/1424-8247/16/9/1280 |
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| author | Dániel Szücs Judit P. Szabó Viktória Arató Barbara Gyuricza Dezső Szikra Imre Tóth Zita Képes György Trencsényi Anikó Fekete |
| author_facet | Dániel Szücs Judit P. Szabó Viktória Arató Barbara Gyuricza Dezső Szikra Imre Tóth Zita Képes György Trencsényi Anikó Fekete |
| author_sort | Dániel Szücs |
| collection | DOAJ |
| description | Although radiolabeled alpha-melanocyte stimulating hormone-analogue NAPamide derivatives are valuable melanoma-specific diagnostic probes, their rapid elimination kinetics and high renal uptake may preclude them from being used in clinical settings. We aimed at improving the pharmacokinetics of radiolabeled DOTA-NAPamide compounds by incorporating a 4-(p-iodo-phenyl)-butanoic acid (IPB) into the molecules. Followed by <sup>68</sup>Ga-, <sup>205/206</sup>Bi-, and <sup>177</sup>Lu-labelling, the radiopharmaceuticals ([<sup>68</sup>Ga]Ga-DOTA-IPB-NAPamide, [<sup>205/206</sup>Bi]Bi-DOTA-IPB-NAPamide, [<sup>177</sup>Lu]Lu-DOTA-IPB-NAPamide) were characterized in vitro. To test the imaging behavior of the IPB-containing probes, B16F10 tumor-bearing C57BL/6 mice were subjected to in vivo microPET/microSPECT/CT imaging and ex vivo biodistribution studies. All tracers were stable in vitro, with radiochemical purity exceeding 98%. The use of albumin-binding moiety lengthened the in vivo biological half-life of the IPB-carrying radiopharmaceuticals, resulting in elevated tumor accumulation. Both [<sup>68</sup>Ga]Ga-DOTA-IPB-NAPamide (5.06 ± 1.08 %ID/g) and [<sup>205/206</sup>Bi]Bi-DOTA-IPB-NAPamide (4.50 ± 0.98 %ID/g) exhibited higher B16F10 tumor concentrations than their matches without the albumin-binding residue ([<sup>68</sup>Ga]Ga-DOTA-NAPamide and [<sup>205/206</sup>Bi]Bi-DOTA-NAPamide: 1.18 ± 0.27 %ID/g and 3.14 ± 0.32; respectively), however; the large amounts of off-target radioactivity do not confirm the benefits of half-life extension for short-lived isotopes. Enhanced [<sup>177</sup>Lu]Lu-DOTA-IPB-NAPamide tumor uptake even 24 h post-injection proved the advantage of IPB-based prolonged circulation time regarding long-lived radionuclides, although the significant background noise must be addressed in this case as well. |
| first_indexed | 2024-03-10T22:16:08Z |
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| language | English |
| last_indexed | 2024-03-10T22:16:08Z |
| publishDate | 2023-09-01 |
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| spelling | doaj.art-239947dec2ce4685ab9b018181f7ad522023-11-19T12:25:09ZengMDPI AGPharmaceuticals1424-82472023-09-01169128010.3390/ph16091280Investigation of the Effect on the Albumin Binding Moiety for the Pharmacokinetic Properties of <sup>68</sup>Ga-, <sup>205/206</sup>Bi-, and <sup>177</sup>Lu-Labeled NAPamide-Based RadiopharmaceuticalsDániel Szücs0Judit P. Szabó1Viktória Arató2Barbara Gyuricza3Dezső Szikra4Imre Tóth5Zita Képes6György Trencsényi7Anikó Fekete8Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, HungaryDivision of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, HungaryDivision of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, HungaryDivision of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, HungaryDivision of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, HungaryDepartment of Physical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, HungaryDivision of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, HungaryDivision of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, HungaryDivision of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, HungaryAlthough radiolabeled alpha-melanocyte stimulating hormone-analogue NAPamide derivatives are valuable melanoma-specific diagnostic probes, their rapid elimination kinetics and high renal uptake may preclude them from being used in clinical settings. We aimed at improving the pharmacokinetics of radiolabeled DOTA-NAPamide compounds by incorporating a 4-(p-iodo-phenyl)-butanoic acid (IPB) into the molecules. Followed by <sup>68</sup>Ga-, <sup>205/206</sup>Bi-, and <sup>177</sup>Lu-labelling, the radiopharmaceuticals ([<sup>68</sup>Ga]Ga-DOTA-IPB-NAPamide, [<sup>205/206</sup>Bi]Bi-DOTA-IPB-NAPamide, [<sup>177</sup>Lu]Lu-DOTA-IPB-NAPamide) were characterized in vitro. To test the imaging behavior of the IPB-containing probes, B16F10 tumor-bearing C57BL/6 mice were subjected to in vivo microPET/microSPECT/CT imaging and ex vivo biodistribution studies. All tracers were stable in vitro, with radiochemical purity exceeding 98%. The use of albumin-binding moiety lengthened the in vivo biological half-life of the IPB-carrying radiopharmaceuticals, resulting in elevated tumor accumulation. Both [<sup>68</sup>Ga]Ga-DOTA-IPB-NAPamide (5.06 ± 1.08 %ID/g) and [<sup>205/206</sup>Bi]Bi-DOTA-IPB-NAPamide (4.50 ± 0.98 %ID/g) exhibited higher B16F10 tumor concentrations than their matches without the albumin-binding residue ([<sup>68</sup>Ga]Ga-DOTA-NAPamide and [<sup>205/206</sup>Bi]Bi-DOTA-NAPamide: 1.18 ± 0.27 %ID/g and 3.14 ± 0.32; respectively), however; the large amounts of off-target radioactivity do not confirm the benefits of half-life extension for short-lived isotopes. Enhanced [<sup>177</sup>Lu]Lu-DOTA-IPB-NAPamide tumor uptake even 24 h post-injection proved the advantage of IPB-based prolonged circulation time regarding long-lived radionuclides, although the significant background noise must be addressed in this case as well.https://www.mdpi.com/1424-8247/16/9/1280albumin-binding moietymalignant melanoma (MM)melanocortin-1 receptor (MC1-R)NAPamidepositron emission tomography (PET)radiolabeling |
| spellingShingle | Dániel Szücs Judit P. Szabó Viktória Arató Barbara Gyuricza Dezső Szikra Imre Tóth Zita Képes György Trencsényi Anikó Fekete Investigation of the Effect on the Albumin Binding Moiety for the Pharmacokinetic Properties of <sup>68</sup>Ga-, <sup>205/206</sup>Bi-, and <sup>177</sup>Lu-Labeled NAPamide-Based Radiopharmaceuticals Pharmaceuticals albumin-binding moiety malignant melanoma (MM) melanocortin-1 receptor (MC1-R) NAPamide positron emission tomography (PET) radiolabeling |
| title | Investigation of the Effect on the Albumin Binding Moiety for the Pharmacokinetic Properties of <sup>68</sup>Ga-, <sup>205/206</sup>Bi-, and <sup>177</sup>Lu-Labeled NAPamide-Based Radiopharmaceuticals |
| title_full | Investigation of the Effect on the Albumin Binding Moiety for the Pharmacokinetic Properties of <sup>68</sup>Ga-, <sup>205/206</sup>Bi-, and <sup>177</sup>Lu-Labeled NAPamide-Based Radiopharmaceuticals |
| title_fullStr | Investigation of the Effect on the Albumin Binding Moiety for the Pharmacokinetic Properties of <sup>68</sup>Ga-, <sup>205/206</sup>Bi-, and <sup>177</sup>Lu-Labeled NAPamide-Based Radiopharmaceuticals |
| title_full_unstemmed | Investigation of the Effect on the Albumin Binding Moiety for the Pharmacokinetic Properties of <sup>68</sup>Ga-, <sup>205/206</sup>Bi-, and <sup>177</sup>Lu-Labeled NAPamide-Based Radiopharmaceuticals |
| title_short | Investigation of the Effect on the Albumin Binding Moiety for the Pharmacokinetic Properties of <sup>68</sup>Ga-, <sup>205/206</sup>Bi-, and <sup>177</sup>Lu-Labeled NAPamide-Based Radiopharmaceuticals |
| title_sort | investigation of the effect on the albumin binding moiety for the pharmacokinetic properties of sup 68 sup ga sup 205 206 sup bi and sup 177 sup lu labeled napamide based radiopharmaceuticals |
| topic | albumin-binding moiety malignant melanoma (MM) melanocortin-1 receptor (MC1-R) NAPamide positron emission tomography (PET) radiolabeling |
| url | https://www.mdpi.com/1424-8247/16/9/1280 |
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